Abstract
Extranodal marginal-zone lymphoma of mucosa-associated lymphoid tissue of the stomach (gastric MALT lymphoma) is derived from memory B cells of the marginal zone. Normal memory B cells do not express markers of germinal-center B cells, such as E2A (immunoglobulin enhancer-binding factor E12/E47), B-cell chronic lymphocytic leukemia/lymphoma 6 (BCL6), or activation-induced cytidine deaminase (AID). E2A is a transcription factor that induces somatic hypermutations and blocks plasma cell differentiation. In 50 stage-I(E)/II(E1) gastric MALT lymphomas, we confirmed that all cases were BCL6(-)/AID(-), but a subset (50%, 25/50) was E2A(+). As E2A(-) and E2A(+) gastric MALT lymphomas had similar numbers of somatic hypermutations without intraclonal variations, which implied an origin from memory B cells, the expression of E2A was best regarded as a marker of aberrant follicular differentiation. Although the status of somatic hypermutation was not affected by E2A, E2A(+) gastric MALT lymphoma showed less plasmacytoid infiltrates and higher expressions of miRNA-223, a microRNA associated with memory B cells. Clinically, E2A(+) gastric MALT lymphomas were more likely to spread to perigastric lymph nodes and were less responsive to Helicobacter eradication therapy than were E2A(-) gastric MALT lymphomas. Taken together, aberrant E2A expression is a diagnostic feature of a subtype of gastric MALT lymphoma with weaker plasmacytoid infiltrates and stronger miR-223 expression. A prospective study would be necessary to verify the association between E2A expression and a poor response to Helicobacter eradication therapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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B-Lymphocytes / chemistry*
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B-Lymphocytes / immunology
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B-Lymphocytes / pathology
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Basic Helix-Loop-Helix Transcription Factors / analysis*
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Biomarkers, Tumor / analysis*
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Biopsy
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Cell Differentiation
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Cluster Analysis
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Cytidine Deaminase / analysis
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DNA-Binding Proteins / analysis
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Gene Expression Regulation, Neoplastic
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Genes, Immunoglobulin Heavy Chain
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Helicobacter Infections / drug therapy
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Helicobacter Infections / microbiology
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Helicobacter pylori / pathogenicity
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Humans
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Immunohistochemistry
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Immunologic Memory*
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Lymph Nodes / chemistry*
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Lymph Nodes / immunology
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Lymph Nodes / pathology
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Lymphoma, B-Cell, Marginal Zone / chemistry*
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Lymphoma, B-Cell, Marginal Zone / genetics
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Lymphoma, B-Cell, Marginal Zone / immunology
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Lymphoma, B-Cell, Marginal Zone / microbiology
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Lymphoma, B-Cell, Marginal Zone / pathology
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Lymphoma, B-Cell, Marginal Zone / therapy
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MicroRNAs / analysis*
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Mutation
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Neoplasm Staging
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Plasma Cells / chemistry*
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Plasma Cells / immunology
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Plasma Cells / pathology
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Proto-Oncogene Proteins / analysis
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Proto-Oncogene Proteins c-bcl-6
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Retrospective Studies
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Reverse Transcriptase Polymerase Chain Reaction
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Stomach Neoplasms / chemistry*
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Stomach Neoplasms / genetics
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Stomach Neoplasms / immunology
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Stomach Neoplasms / microbiology
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Stomach Neoplasms / pathology
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Stomach Neoplasms / therapy
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Taiwan
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Treatment Outcome
Substances
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BCL6 protein, human
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Basic Helix-Loop-Helix Transcription Factors
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Biomarkers, Tumor
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DNA-Binding Proteins
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MIRN223 microRNA, human
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MicroRNAs
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-6
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TCF3 protein, human
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TCL1A protein, human
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AICDA (activation-induced cytidine deaminase)
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Cytidine Deaminase